Deep venous thrombosis and pulmonary embolism

All surgical patients are at risk for the development of deep venous thrombosis and subsequent pulmonary embolism or postphlebitic syndrome. The evolution of ultrasonographic imaging has increased the awareness of prevention, diagnosis, and treatment of deep venous thrombosis. Duplex imaging and Doppler color flow imaging have made the diagnosis of deep venous thrombosis relatively simple, painless, inexpensive, and definitive. These procedures have gained acceptance by both patients and physicians. Several risk factors have been identified that increase the chance of the development of deep venous thrombosis. These factors include a history of deep venous thrombosis, presence of a malignant process, increasing age, cigarette smoking, obesity, prolonged bed rest, and general anesthesia. The greater the number of risk factors, the more aggressive prophylaxis should be. Means of prophylaxis have improved, and surgeons now generally agree that some form of prophylaxis is required. Heparin and intermittent compression devices appear to be equally effective in preventing deep venous thrombosis. The addition of venous monitoring in high-risk patients permits immediate identification of the presence of deep venous thrombosis. During the last decade, the treatment of patients with deep venous thrombosis has changed little. Heparin followed by warfarin remains the treatment of choice. A small group of patients receive fibrinolytic therapy for deep venous thrombosis. Although the incidence of postoperative deep venous thrombosis has decreased during the last decade, it remains a significant complication.     

NPY hyperinnervation in Hirschsprung's disease: both adrenergic and nonadrenergic fibers contribute.

In Hirschsprung's disease, the aganglionic bowel is characterized by an absence of ganglion cells and an increased number of adrenergic and presumed cholinergic nerve fibers. In addition, a severe derangement of peptide-containing nerve fibers is encountered including a hyperinnervation of neuropeptide Y (NPY)-containing fibers. Using immunochemical and immunocytochemical methods, we examined the nature of the NPY-containing nerve fibers contributing to the hyperinnervation. The concentration of NPY was markedly increased in the aganglionic segment. Coexistence of NPY, vasoactive intestinal peptide (VIP), and the adrenergic enzyme tyrosine hydroxylase (TH) showed small populations of nerve fibers containing NPY/TH, NPY/VIP, or TH alone in ganglionic intestine. Numerous nerve fibers stored VIP but lacked NPY. These fibers did not contain TH, indicating that all VIP-containing fibers are nonadrenergic. In the aganglionic intestine there was a marked increase in the number of nerve fibers storing NPY/TH and NPY/VIP, whereas the fibers storing VIP alone were reduced in number. A small number of nerve fibers storing NPY alone occurred in the hypertrophic nerve bundles. NPY/VIP-containing nerve fibers were particularly numerous in the mucosa in aganglionic intestine, which may be of interest in the diagnosis of Hirschsprung's disease allowing the use of mucosal biopsy specimens. Thus, the proliferating NPY-containing nerve fibers in the aganglionic intestine seem to comprise three different populations, one adrenergic and two nonadrenergic, one of which contains in addition VIP.     

Studies of pickled vegetables and cause of esophageal cancer in Linxian. II. Determination of nitrosamines and their precursors]

Pickled vegetables are daily food consumed in the high-risk areas for esophageal cancer in China. We analyzed the nitrosamine content of Linxian pickles by GC/TEA and found that trace amounts of six nitrosamines (NDMA, NDEA, NMBA, NMAMBA, NDPA, NPYR) were present, with the highest concentrations being NDMA and NDEA (1.7 and 1.9 micrograms/kg wet weight respectively). The average level of nitrosamine precursors, such as nitrate (111.22 mg/L), nitrite (0.152 mg/L) and secondary amines (4.223 mg/L), in pickled vegetables were determined, and their pH values ranged from 3 to 5.     

Transport of estrogen-induced oxytocin receptors in the ventromedial hypothalamus.

The modulation of oxytocin (OT) receptors (OTRs) by estrogen was investigated in the ventromedial hypothalamus by in vitro receptor autoradiography. Treatment of ovariectomized and adrenalectomized rats with various doses of estradiol benzoate (EB) increased OTR binding not only in the ventromedial nuclei of the hypothalamus (VMN), but also in the area lateral to the nuclei (IVMN). After a single injection of EB, OTRs first were induced within the ventrolateral parts of the VMN, and only hours later they appeared in the IVMN. This is consistent with the interpretation that OTRs are first induced within the estrogen-sensitive neurons of the ventrolateral VMN and then are transported laterally out of the nuclei. Two additional experiments confirmed this interpretation. First, local infusion of a low dose (10 micrograms) of the neuronal transport inhibitor vinblastine blocked the appearance of OTRs in the IVMN but did not prevent the induction of OTRs by EB within the nuclei. Second, a knife cut placed lateral to the VMN prevented the spread of OTRs out of the nuclei. However, even after treatment with a high dose of EB (2 x 10 micrograms), progesterone (P) was required for a maximal extension of the area covered by OTRs. Thus, the OTR is an estrogen-induced neurotransmitter receptor that is transported to its site of action, the lateral ventromedial hypothalamus, where it is modulated by P and where estrogen-induced OT immunoreactivity is found.     

Regulatory properties of brain glutamate decarboxylase (GAD): the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain

The apoenzyme of glutamate decarboxylase [enzyme without bound cofactor, pyridoxal 5'-phosphate (pyridoxal-P)] serves as a reservoir of inactive glutamate decarboxylase (GAD) that can be activated when additional GABA synthesis is required. We have investigated which of two molecular forms of GAD is present as apoenzyme in synaptosomes and in cortex, caudate nucleus, hippocampus, and cerebellum of rat brain. Endogenous glutamate apodecarboxylase (apoGAD) was labeled by incubating extracts of synaptosomes or punches of each region with 32P-pyridoxal-P, followed by reduction with NaBH4, to link covalently the 32P-pyridoxal-P to GAD. Proteins were separated by SDS-PAGE. Punches from all four brain regions and forebrain synaptosomes contained two forms of GAD with apparent Mrs of 63 and 65 kDa as identified by immunoblotting with four antiGAD sera. Punches and synaptosomes contained a major 32P-pyridoxal-P-labeled band with an apparent Mr of 63 kDa that was stained on immunoblots by the antiGAD serum 1440 and the monoclonal antibody GAD-6, and a minor labeled band at 65 kDa that was stained by the 1440, 6799, and K2 antisera. Synaptosomes contained remarkably few other strongly labeled proteins, but punches contained several other labeled bands. Three additional lines of evidence indicate that the labeled 63-kDa protein is apoGAD: (1) it was purified by immunoaffinity chromatography with the GAD-1 monoclonal antibody; (2) it yielded one major labeled peptide when digested with chymotrypsin, and that peptide appeared identical in peptide-mapping experiments to the labeled active-site peptide isolated from chromatographically prepared rat brain GAD; and (3) its labeling was selectively blocked by 4-deoxypyridoxine 5'-phosphate, a competitive inhibitor of the binding of pyridoxal-P to GAD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double-blind, placebo-controlled comparison of clonazepam and alprazolam for panic disorder

To test the reported antipanic efficacy of clonazepam, the authors randomized 72 subjects with panic disorder to 6 weeks of treatment with either alprazolam, clonazepam, or placebo. Endpoint analysis demonstrated a significant beneficial effect of both active treatments, but not placebo treatment, on the frequency of panic attacks, overall phobia ratings, and the extent of disability. Comparison of the two active treatments revealed no significant differences and no consistent tendency for one agent to be favored over another, although power to detect small differences was limited. Sedation and ataxia were the most common side effects reported, but these effects were mild and transient and did not interfere with treatment outcome. The results of this double-blind, placebo-controlled trial are consistent with previous reports of clonazepam's antipanic efficacy.     

Transneuronal degeneration of thalamic neurons following deafferentation: quantitative studies using [3H]thymidine autoradiography.

Transneuronal degeneration of thalamic neurons following partial deafferentation was studied using [3H]thymidine autoradiography. Timed-pregnant female Sprague-Dawley rats received systemic injections of [3H]thymidine on embryonic day (E) 13, 14 and/or 15. On the day of birth, pups were anesthetized by hypothermia and subjected to unilateral enucleation, unilateral removal of the inferior colliculus or sham lesion. Animals were sacrificed on postnatal day 10 or 30 and the brains processed for autoradiography. Material from sham-lesioned animals demonstrates that neurons destined for the dorsal lateral geniculate nucleus (LGd) undergo final mitoses on E13, 14 and 15. Neurons in the ventral medial geniculate nucleus (MGv) undergo final mitoses on E13 and 14. Thirty days following neonatal unilateral eye removal, the contralateral LGd displays a loss of approximately 30-35% of [3H]thymidine labeled neurons. Neonatal unilateral removal of the inferior colliculus results in a loss of approximately 30-40% of labeled neurons in MGv. For both LGd and MGv, shorter survival times reveal less severe cell loss. Late generated (E15) LGd neurons show less severe loss following enucleation than do earlier generated neurons. These results document the degree of cell loss in sensory thalamic nuclei following deafferentation and demonstrate that [3H]thymidine autoradiography provides a useful quantitative method for assessing anterograde transneuronal cell loss in targeted populations of neurons in the developing central nervous system.     

Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products

The experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.